Specific Treatment Recommendations Research Articles

The Ambiguous Loss of Singlehood: Conceptualizing and Treating Singlehood Ambiguous Loss Among Never-Married Adults

Ambiguous loss theory provides a framework for conceptualizing and treating singlehood ambiguous loss among adults who desire to be in a long-term committed romantic relationship, such as marriage, but have never been in such a relationship. Adults who have never married may experience an ambiguous loss due to the lack of clear information as to whether their anticipated spouse, who is psychologically present yet physically absent, will materialize at some point. This lack of clear information about an indefinitely missing anticipated spouse tends to create ambivalence about holding on to the prospect that the anticipated spouse will materialize versus moving on through accepting and grieving the loss of the non-materialized anticipated spouse. The absence of rituals for demarcating singlehood ambiguous loss may increase ambivalence. The degree of ambivalence experienced from adult singlehood ambiguous loss likely varies according to the developmental timing of singlehood, decisions between settling and indefinite singlehood, unviable potential spouses, and non-materialized children. Specific treatment recommendations (i.e., avoiding contraindicated treatment approaches, implementing an informed not-knowing stance, and fostering dialectical thinking) and specific interventions for adapting the established treatment for ambiguous loss (i.e., increasing resilience through normalizing ambivalence, tempering mastery, finding meaning, reconstructing identity, revising attachment, and discovering hope) for clients struggling with the ambiguous loss of singlehood are presented.

The Role of Sympatho-Inhibition in Combination Treatment of Obesity-Related Hypertension.

Obesity-related hypertension is commonly characterized by increased sympathetic nerve activity and is therefore acknowledged as a predominantly neurogenic form of hypertension. The sustained sympatho-excitation not only contributes to the rise in blood pressure but also elicits a vicious cycle which facilitates further weight gain and progression of associated co-morbidities. While weight loss and exercise remain at the forefront of therapy for obesity and obesity-related hypertension, the difficulties in achieving and maintaining long-term weight loss with lifestyle measures and the variable blood pressure response to weight loss often necessitate prescription of antihypertensive drug therapy. Remarkably, there are no specific recommendations for pharmacologic treatment for obese patients with arterial hypertension in any of the current guidelines and general principles of antihypertensive treatment are applied. The use of β-blockers and diuretics is commonly discouraged as first- or second-line therapy due to their unfavorable metabolic effects. This review explores evolving therapeutic strategies which based on their interference with pathophysiologic mechanism relevant in the context of obesity may guide optimized treatment of obesity-related hypertension.

Die schweregradorientierte Therapie der Spondylodiszitis – eine prospektive Betrachtung anhand von elektronisch basierten Behandlungspfaden

Spondylodiscitis is a rare but serious infection of the spine. Recognised methods of treatment include immobilisation and systemic antibiotics. However, available data for specific and recommendations for continuing treatment are also rare. The aim of the present study is the optimisation of the therapy of spondylodiscitis using a clinical pathway that depends on a classification of spondylodiscitis. From 1 October 1998 to 31 December 2013, a classification of the severity of spondylodiscitis was established, including specific treatment recommendations. As part of the re-evaluation, the classification of severity was adapted. On this basis, electronically based clinical pathways were developed. A total of 296 cases were included. With a steadily increasing number of treatments, the mean age of the patients increased to 67.3 years. In 34.3% of these patients, spondylodiscitis developed spontaneously and 68.6% of patients did not receive treatment until the diagnosis. In the context of the specific treatment, pain intensity decreased from 6.0 to 3.1 NRS (numeric rating scale). The inflammatory values (CRP) decreased from 119.2 to 46.7 mg/dl. The time from the onset of symptoms to the surgical treatment was almost 65.6 days and has not changed significantly. Nevertheless, the time from admission to surgical treatment could be reduced to less than 3 days. The classification of patients into 3 degrees of severity of spondylodiscitis (SSC) depends on the SponDT: spondylodiscitis diagnosis and treatment. The SponDT describes vertebral destruction and the current neurological status. The severity-adapted therapy was mapped electronically and includes specific surgical care, systemic antibiotic therapy and physical therapy.

Characteristics and clinical treatment of tobacco smokers enrolled in a VA substance use disorders clinic

Individuals with a substance use disorder (SUD) diagnosis are more than twice as likely to smoke cigarettes as the general population. Emerging research has suggested that treating a substance use disorder simultaneously with tobacco use leads to a higher rate of treatment success for both substances. Despite this, substance use treatment protocols tend not to focus on tobacco use; in fact, traditional substance use treatments often discourage patients from attempting to quit smoking. One rationale is that patients may not be motivated to quit smoking. In the current study, data from veterans enrolled in outpatient treatment for a SUD were examined to assess for general characteristics of smokers as compared to non-smokers as well as to examine motivation to quit smoking. Baseline (i.e., pre-treatment) data from 277 Veterans were used. Charts of smokers in the SUD clinic (SUDC) were reviewed to assess how smoking is handled by SUDC providers, and if smokers attempt cessation. Of 277, 163 (59%) SUDC patients reported that they currently smoke cigarettes (M=16.3 cigarettes per day, SD=11.1). Smokers in the clinic reported greater general impairment than nonsmokers on the Short Index of Problems, F(1248)=8.9, p=0.003, as well as greater specific impairment: Physical Problems, F(1258)=13.5, p=0.000; Interpersonal Problems, F(1262)=5.6, p=0.019; Intrapersonal Problems, F(1260)=6.5, p=0.011, and Social Responsibility, F(1262)=14.7, p=0.000. Smokers in the sample were marginally more anxious than their non-smoking counterparts as measured by the GAD-7, F(1254)=4.6, p=0.053, though they were not significantly more depressed (p=0.19). On a 1–10 scale, smokers reported moderate levels of importance (M=5.4, SD=3.1), readiness (M=5.6, SD=3.2), and confidence (M=5.0, SD=3.0) regarding quitting smoking. Review of smokers' medical records reveal that while SUDC providers assess tobacco use at intake (90%) and offer treatment (86.5%), a substantially small portion of smokers attempt cessation (41.1%) while enrolled in SUDC. Moreover, no patients were enrolled in smoking-specific behavioral interventions while in SUDC, though 78 patients did obtain nicotine replacement or another smoking cessation medication (41% were prescribed by a SUDC provider). Contrary to the belief that treatment-seeking substance users are not motivated to quit smoking, these preliminary analyses demonstrate that Veterans were at least contemplating quitting smoking while they were enrolled in substance use treatment. Further, there is evidence that cigarette smokers have greater impairment caused by substance use, suggesting that this subgroup is of particular high need. Specific treatment recommendations are discussed, including how behavioral health providers in SUD clinics may be better able to capitalize on patients' moderate motivation to quit at intake.

1563P - Literature review of TPOR agonists for CIT

Background: Chemotherapy-induced thrombocytopenia (CIT) can lead to dose delay/reduction. Currently there are no specific treatment recommendations beyond transfusion. We performed a systematic literature search on the use of thrombopoietin receptor (TPOR) agonists for CIT. Methods: We searched the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed, EMBASE, clinicaltrials.gov, and Health Technology Assessments from 1995-2017 for studies of TPOR agonists [eg, romiplostim, eltrombopag, TPO, and megakaryocyte growth and development factor (MGDF)] for CIT. Each publication was independently reviewed by two people and data extracted into Excel. Results: We screened 892 titles/abstracts, assessed 52 articles, and abstracted data from 14 articles and 15 abstracts/posters from 1997-2016 (10 TPO, 7 MGDF, 8 romiplostim, and 4 eltrombopag), which included 18 randomized trials. TPOR agonist regimens varied widely. Common cancers included leukemia/lymphoma (n = 8 studies) and non-small cell lung cancer (n = 4), and common chemotherapies were platinum-based (n = 15) or included cytarabine (n = 5). Median or mean baseline platelet counts were 56 × 109/L-324 × 109/L in studies to treat CIT (N = 7) and 109 × 109/L-597 × 109/L in studies to prevent CIT (N = 22). The 16 placebo-controlled or crossover studies (MGDF n = 6 studies, TPO n = 5, romiplostim n = 3, eltrombopag n = 2) generally found that TPOR agonists increased platelet counts and reduced transfusions and dose delays/reductions (Table). Safety measures included thromboses (n = 19 studies) and bleeding (n = 8).Table1563P Study Design and Endpoints TPOR Agonist vs. Control (Range study incidences)CIT Prevention: Vs. Placebo/Observation or Crossover (n = 16 studies)TPOR Agonist (N = 625)Control (N = 428)Efficacy EndpointChemotherapy dose delay/reduction3% - 40%58% - 75%Grade 3-4 thrombocytopenia0% - 100%0% - 42%Platelet transfusions6% - 58%8% - 83%Safety EndpointThrombosis0% - 29%0% - 33%Bleeding0% - 100%0% - 50%CIT Treatment: Vs. rhIL-11 (n = 2 studies)TPOR Agonist (N = 63)Control (N = 71)Efficacy EndpointChemotherapy dose delay/reductionN/AN/AGrade 3-4 thrombocytopeniaGrade 3: 54% Grade 4: 14%Grade 3: 85% Grade 4: 41%Platelet transfusions11%30%Safety EndpointThrombosisN/AN/ABleedingN/AN/ACIT Treatment: Vs. PBO/Observation or Crossover (n = 2 studies)TPOR Agonist (N = 172)Control (N = 65)Efficacy EndpointChemotherapy dose delay/reductionN/AN/AGrade 3-4 thrombocytopeniaN/AN/APlatelet transfusionsN/AN/ASafety EndpointThrombosis5% - 13%7% - 21%Bleeding2% - 9%9% Open table in a new tab Conclusions: While TPOR agonists have not been approved for use in CIT, this literature review suggests that TPOR agonists may increase platelet counts and decrease chemotherapy dose delay/reduction. Further study with well-characterized bleeding and platelet thresholds is needed to explore the possible benefits of TPOR agonists for CIT compared with current care options (eg, transfusions, dose reduction). Legal entity responsible for the study: Amgen Inc. Funding: Amgen Inc. Disclosure: G.A. Soff: Research support from Amgen. J. Fryzek: Employee of EpidStat, which serves as a consultant with Amgen. M. Mullins: Consultant for EpidStat, which itself consults for Amgen. L.C. Bylsma: Employee of EpidStat, which consults for Amgen. J.K. Park: Amgen employee. All other authors have declared no conflicts of interest.

Psychiatric comorbidity in alcohol use disorders: results from the German S3 guidelines.

Alcohol use disorders (AUD) have a high comorbidity with mental disorders. Vice versa, alcohol consumption plays an important role in affective disorders, anxiety disorders, ADHD, schizophrenic psychosis, and other mental disorders. In developing the current interdisciplinary, evidence-based treatment guideline on screening, diagnostics, and treatment of AUD, available research on comorbid mental diseases in AUD has been compiled to generate recommendations for treatment. The guideline was prepared under the responsibility of the German Association for Psychiatry, Psychotherapy, and Psychosomatics (DGPPN) and the German Association for Addiction Research and Therapy (DG-Sucht). To meet the methodological criteria for the highest quality guidelines ("S3-criteria") as defined by the Association of Scientific Medical Societies in Germany (AWMF), the following criteria were employed: (1) a systematic search, selection, and appraisal of the international literature; (2) a structured process to reach consensus; and (3) inclusion of all relevant representatives of future guideline users. After assessing and grading the available literature, the expert groups generated several recommendations for the screening, diagnosis, and treatment of comorbid mental disorders. These recommendations were subdivided into psycho-, pharmaco-, and combination therapies. These are the first guidelines ever to make specific treatment recommendations for comorbid mental diseases in AUD. The recommendations extend to different treatment approaches including diagnostics and settings to present available effective and state-of-the-art treatment approaches to clinicians. Hitherto, many clinical constellations have not been addressed in research. Therefore, recommendations for future research are specified.

Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.

Targeted resequencing gene panels are used in the diagnostic setting to identify gene defects in epilepsy. We performed targeted resequencing using a 30-genes panel and a 95-genes panel in 349 patients with drug-resistant epilepsies beginning in the first years of life. We identified 71 pathogenic variants, 42 of which novel, in 30 genes, corresponding to 20.3% of the probands. In 66% of mutation positive patients, epilepsy onset occurred before the age of 6 months. The 95-genes panel allowed a genetic diagnosis in 22 (6.3%) patients that would have otherwise been missed using the 30-gene panel. About 50% of mutations were identified in genes coding for sodium and potassium channel components. SCN2A was the most frequently mutated gene followed by SCN1A, KCNQ2, STXBP1, SCN8A, CDKL5, and MECP2. Twenty-nine mutations were identified in 23 additional genes, most of them recently associated with epilepsy. Our data show that panels targeting about 100 genes represent the best cost-effective diagnostic option in pediatric drug-resistant epilepsies. They enable molecular diagnosis of atypical phenotypes, allowing to broaden phenotype-genotype correlations. Molecular diagnosis might influence patients' management and translate into better and specific treatment recommendations in some conditions.

Analysis of an Online Decision Support Tool for Chronic Lymphocytic Leukemia: Disparities in Treatment Selection Between Experts and Community Practitioners

Background. Rapid advances in clinical discovery and availability of new treatment options have increased the complexity of treatment decisions for patients with CLL. Guidelines list multiple agents and combinations as recommended therapeutic options for CLL but often do not provide specific treatment recommendations for individual patients. We developed an online treatment decision tool that provides treatment recommendations from CLL experts for specific patient cases. We hypothesized that these individualized recommendations from recognized experts would affect treatment plans. Here we report on an analysis of data entered into this CLL decision support tool, including variance between intended treatment of tool users and the recommendations made by the experts and the impact of the tool on subsequent therapy decisions.Methods. In December 2015, 5 experts provided treatment recommendations for 1380 case variations based on key factors that guide treatment choice. Expert-selected factors for newly diagnosed CLL included age, fitness (based on ECOG PS, CIRS, and renal function), and cytogenetic abnormalities (del[17p], del[11q], or other). Additional variables for patients with relapsed/refractory (R/R) disease after first-line treatment included previous treatment, response duration, and burden of comorbidities. To use the tool, drop-down menus allowed users to select from choices for each variable and their intended treatment for that patient. The corresponding treatment selection from 5 experts was then displayed and users were asked about the tool's impact on their planned treatment.Results. An analysis of 883 patient scenarios (67% treatment naive and 33% with R/R CLL) entered into the tool from February 2016 through July 2016 found substantial variation between the intended therapy choice among tool users and the recommendations from the experts.For example, in every patient case with del(17p), all 5 of the experts recommended ibrutinib as first-line therapy whereas only 49% of tool users planned to use ibrutinib for these patients. Of those users whose intended first-line therapy for del(17p) CLL did not match the experts' recommendation, 54% indicated that this tool would change their original treatment plan and 17% indicated a barrier to implementing this treatment. For either elderly or unfit patients without del(17p), 4 of 5 experts recommended obinutuzumab plus chlorambucil, but only 41% of tool users planned to use this regimen with 50% citing barriers to this treatment approach.For patients with del(17p) CLL and disease relapse or recurrence after chemoimmunotherapy, all 5 experts recommended ibrutinib for these cases with the exception of patients with a history of atrial fibrillation, anticoagulation, or difficult-to-control hypertension where 4 of 5 experts recommended idelalisib/rituximab. Again, the intended treatment plan of approximately 50% of tool users failed to match the experts' recommendation for these cases, and half of these users indicated that this tool would change their original treatment plan. At the time of tool development, all experts recommended either idelalisib/rituximab or clinical trial for patients with R/R CLL and del(17p) who previously received ibrutinib, but 61% of users indicated that they were unsure of the next appropriate treatment. All users who answered the impact question indicated that they now intended to use the expert-recommended treatment for these patients.For patients without del(17p) cytogenetics, treatment selection was more variable among experts and users and changed based on age, fitness, and previous therapy. For patients with del(11q) or other cytogenetics, approximately 20% of tool users were unsure of the appropriate treatment after progression on first-line therapy but 71% of those who answered the impact questions indicated that they remained unsure of their treatment approach despite viewing expert recommendations.Conclusions. Our analysis demonstrates that this interactive online therapy decision tool providing expert recommendations for specific case scenarios in CLL can support optimal decision making and change intended treatment for a majority of cases in which the planned therapy differed from the experts. Detailed comparisons of expert and user responses from the online tool will be presented. DisclosuresAwan:Innate Pharma: Research Funding; Pharmacyclics: Consultancy; Novartis Oncology: Consultancy. Barrientos:AbbVie: Consultancy, Research Funding; Janssen: Consultancy; Gilead: Consultancy, Research Funding. Coutre:AbbVie: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Research Funding. Zelenetz:Gilead Sciences: Research Funding.

Well-Differentiated, Non-Functional, Non-Ampullary Duodenal Neuroendocrine Tumors: Toward Defining Evaluation and Management.

Nonfunctional, non-ampullary duodenal neuroendocrine tumors (dNETs) are rare neoplasms, and specific treatment recommendations are less clear than for other NETs. We performed a retrospective review of patients (pts) with a diagnosis of dNET, excluding hormonally functional, ampullary, and high-grade tumors. Clinical data were evaluated to identify factors that might impact clinical staging and predictors of metastases. Thirty-six pts were identified. Surgical resection was performed in 28 and endoscopic resection in 8. LNs were included in specimens of 19/28 (68%) pts who underwent surgical resection (median #LNs 5, range 1-12). Of these 19 pts, 5 (26%) were found to be LN+. Of LN+ pts, all had tumors ≤2cm. When compared to LN- pts, LN+ pts were more likely to have muscularis propria (MP) invasion (80 vs. 23%, p=0.04). Tumor size, tumor grade, lymphovascular invasion, and multifocality were similar between LN+ and LN- patients. No pt was found to have distant metastases. Heterogeneity in clinical staging modalities and small number of pts evaluated prohibited meaningful analysis of most appropriate preoperative imaging. At a median follow-up of 25months (range 9-139), no patient developed recurrence or experienced disease-specific death. Non-functional, non-ampullary dNETs, particularly those with MP invasion, have a propensity to metastasize to regional LNs. However, these neoplasms appear to have a favorable prognosis. Further evaluation of preoperative imaging is required to better determine most appropriate clinical staging. A suggested workup and management strategy for prospective evaluation is proposed.

Tumor necrosis factor-alpha blockade with etanercept improves autonomic dysfunction in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease associated with autonomic neuropathy. There is no specific treatment recommendation for autonomic neuropathy (AN) in rheumatic diseases. In addition, there is no study demonstrating therapeutic efficacy of TNF-inhibitor (TNFi) etanercept on autonomic neuropathy in RA. This is the first reported observation of improvement in AN with blockade of TNFi-etanercept in RA. We report a case of a 46-year-old female with severe disease activity treated with subcutaneous etanercept 50mg once a week along with methotrexate 15 mg/week. A significant improvement in cardiovascular autonomic neuropathy and sudomotor function was noted after 6 weeks of treatment.

Physical Training and Activity in People With Diabetic Peripheral Neuropathy: Paradigm Shift.

Diabetic peripheral neuropathy (DPN) occurs in more than 50% of people with diabetes and is an important risk factor for skin breakdown, amputation, and reduced physical mobility (ie, walking and stair climbing). Although many beneficial effects of exercise for people with diabetes have been well established, few studies have examined whether exercise provides comparable benefits to people with DPN. Until recently, DPN was considered to be a contraindication for walking or any weight-bearing exercise because of concerns about injuring a person's insensitive feet. These guidelines were recently adjusted, however, after research demonstrated that weight-bearing activities do not increase the risk of foot ulcers in people who have DPN but do not have severe foot deformity. Emerging research has revealed positive adaptations in response to overload stress in these people, including evidence for peripheral neuroplasticity in animal models and early clinical trials. This perspective article reviews the evidence for peripheral neuroplasticity in animal models and early clinical trials, as well as adaptations of the integumentary system and the musculoskeletal system in response to overload stress. These positive adaptations are proposed to promote improved function in people with DPN and to foster the paradigm shift to including weight-bearing exercise for people with DPN. This perspective article also provides specific assessment and treatment recommendations for this important, high-risk group.

Hypertension and ethnicity.

Despite its continued increase in prevalence in minorities, data regarding hypertension (HTN) control among such ethnic groups remains limited. This review highlights the most recent literature on the epidemiology, prevalence, and treatment strategies of HTN among four racial groups (non-Hispanic Whites (NHW), Blacks, Hispanics, and Asians). Overall awareness and treatment of HTN were found to be higher in blacks when compared with NHWs. Access to health insurance is associated with successful HTN control, particularly among the Hispanic populations. Recent data from SBP Intervention Trial suggests the blood pressure control and adherence rates in blacks were highest among men, with a higher number of comorbidities, and on diuretic therapy. Additionally, the initiation of thiazide-type diuretics and calcium channel blocker was superior to β-adrenergic blockers and angiotensin converting enzyme inhibitor/angiotensin receptor blockers in blood pressure lowering among blacks. However, no specific treatment recommendations exist for Hispanics or Asians. Finally, recent guidelines from the Joint National Commission recommend initial treatment with a thiazide-type diuretic regardless of race. Despite recent progress, racial disparities in awareness and treatment of HTN continue to exist. To reduce this important gap, future research should focus on epidemiologic, genetic, and sociologic factors as well as specific therapies to achieve maximum medical benefit in these subgroups.

Hyponatremia in patients with chronic kidney disease.

Hyponatremia is a common condition encountered in clinical practice. A number of studies have associated low serum sodium levels with increased mortality in various patient populations, such as hospitalized patients and patients with various comorbid conditions; recent studies have shown that individuals with chronic kidney disease also are afflicted by hyponatremia. However, few studies have focused on patients with hemodialysis. Evidence supporting the incidence and prevalence of hyponatremia, clinical characteristics and the association with patient outcomes with hemodialysis is limited. In the present review, we examined the physiology and pathophysiology of water and sodium balance with a special emphasis on changes occurring during end-stage renal disease. The outcomes in patients undergoing hemodialysis were associated with low serum sodium. We evaluated the associations between hyponatremia and mineral bone abnormalities and discussed the elevated incidence and prevalence of difficult clinical outcomes associated with hyponatremia. We also provided specific recommendations for hemodialysis treatment in hyponatremic patients.

Exacerbation of Anxiety and Depression Symptoms following Concussion in a High School Softball Athlete.

HISTORY: A 16-year-old female softball athlete with a history of pre-pubertal migraines sustained a concussion while doing hill sprints. The injury coincided with a loss of consciousness and anterograde amnesia of 20-30 minutes. She presented to clinic six weeks post-injury with symptoms including headache, academic difficulty, and mood lability. Sleep habits were stable, though quality was reported as poor. Headaches occurred daily with variable intensity, were predominately frontal, and were exacerbated by cognitive effort and bright lights. A previously high-achieving student, she experienced difficulty in her classes, particularly foreign language studies. Patient reported pre-injury mood was poor, but had become more irritable than usual with frequent mood swings. Friends and family commented on her increased irritability. Social history significant for death of mother two years previously. PHYSICAL EXAMINATION: Accommodation insufficiency and difficulty with smooth pursuit on visual examination. Cervical spine tenderness and reproduction of headache with palpation. Otherwise normal neurologic and musculoskeletal exams. DIFFERENTIAL DIAGNOSIS: 1.Post-concussion syndrome with visual dysfunction 2.Depression or anxiety disorder exacerbated by trauma TESTS AND RESULTS: Sensory Organization Test: -Composite score of 68 - abnormal Visual domain. Computerized neurocognitive testing: -Composite score of 48 (baseline 105). -Multiple domains affected. Patient Health Questionnaire-9: -12 of 27 (baseline 7). -21% age-adjusted positive predictive value for depressive disorder. Generalized Anxiety Disorder-7: -12 of 21 (baseline 9). -Increased risk of generalized anxiety disorder. Buffalo College Treadmill Testing: -Maximum heart rate of 160. -No symptom exacerbation. FINAL WORKING DIAGNOSIS: Post-concussion syndrome with predominately neuropsychiatric and visual dysfunction likely contributing to headache and cognitive difficulties. TREATMENT AND OUTCOMES: 1. Referral for full neuropsychological evaluation to assess cognitive function and mood disorder and provide specific recommendations for treatment. 2. Physical Therapy for possible cervicogenic component of headaches. 3. Visual assessment and rehabilitation with neuro-optometrist.

Educational Antimicrobial Stewardship Strategies

Educational interventions to improve prescriber and patient knowledge of appropriate antibiotic use are a key component of successful antimicrobial stewardship campaigns in diverse healthcare settings. Provider education may be an impactful strategy for reducing unnecessary prescribing of antibiotics for respiratory tract infections and asymptomatic bacteriuria. Educational interventions designed to improve adherence to prescribing guidelines are more consistently able to impact prescribing of a specific class of medications (e.g., third generation cephalosporins, fluoroquinolones) than overall adherence to a set of specific treatment recommendations. Further research is needed to assess the independent impact of educational programs in bundled stewardship efforts and the duration of their effect on prescribing. Facilitating evidence-based discussions on antimicrobial use between patients and providers has been shown to reduce inappropriate prescribing. However, the impact of these programs on other important metrics in primary care, including duration of physician-patient time, wait times, and number of return office visits, has not been addressed. Educational campaigns in non-clinical settings may be effective ways to educate adults and children on principles of antimicrobial stewardship. Future studies should examine the impact of education outside of the physician’s office on future patient behavior.

Mortality Risk for Acute Cholangitis (MAC): a risk prediction model for in-hospital mortality in patients with acute cholangitis.

BackgroundAcute cholangitis is a life-threatening bacterial infection of the biliary tract. Main focus of this study was to create a useful risk prediction model that helps physicians to assign patients with acute cholangitis into different management groups.Methods981 cholangitis episodes from 810 patients were analysed retrospectively at a German tertiary center.ResultsOut of eleven investigated statistical models fit to 22 predictors, the Random Forest model achieved the best (cross-)validated performance to predict mortality. The receiver operating characteristics (ROC) curve revealed a mean area under the curve (AUC) of 91.5 %. Dependent on the calculated mortality risk, we propose to stratify patients with acute cholangitis into a high and low risk group. The mean sensitivity, specificity, positive and negative predictive value of the corresponding optimal cutpoint were 82.9 %, 85.1 %, 19.0 % and 99.3 %, respectively. All of these results emerge from nested (cross-)validation and are supposed to reflect the model’s performance expected for external data. An implementation of our risk prediction model including the specific treatment recommendations adopted from the Tokyo guidelines is available on http://www2.imse.med.tum.de:3838/.ConclusionOur risk prediction model for mortality appears promising to stratify patients with acute cholangitis into different management groups. Additional validation of its performance should be provided by further prospective trails.

Approval of psychotherapy and medication for the treatment of mental disorders over the lifespan. An age period cohort analysis.

Previous cross-sectional studies revealed inconsistent results regarding mental health treatment preferences among the general population. In particular, it is unclear to what extent specific age groups approve psychotherapy or psychotropic medication for the treatment of mental disorders. We explore whether treatment recommendations of either psychotherapy or psychiatric medication change over the lifespan which includes age-related effects due to increasing age of a person, cohort effects that reflect specific opinions during the time a person was born and period effects that reflect societal changes. Using data from three identical population surveys in Germany from 1990, 2001 and 2011 (combined n = 9046), we performed age-period-cohort analyses to determine the pure age, birth cohort and time period effects associated with the specific treatment recommendations for a person with either depression or schizophrenia, using logistic Partial Least-Squares regression models. For both disorders, approval of both psychotherapy and medication for a person with mental illness increases with age. At the same time, younger cohorts showed stronger recommendations particularly for psychotherapy (OR around 1.07 per decade). The strongest effects could be observed for time period with an increase in recommendation between 1990 and 2001 with odds ratio of 2.36 in depression and 2.97 in schizophrenia, respectively. In general, the treatment option that showed the strongest increase in recommendation was medication for schizophrenia and psychotherapy for depression. Underutilisation of psychotherapy in old age seems not to reflect treatment preferences of older persons. Thus, special treatment approaches need to be offered for this group that seems to be willing for psychotherapy but do not yet use it. Cohort patterns suggest that approval of psychotherapy among older persons will likely further increase in the coming years as these people get older. Finally, strong period effects underpin the importance of changing attitudes in the society. These could reflect reporting changes about psychiatric topics in the media or a general increase in the perception of treatment options. Nevertheless, more treatment offers especially for older people are needed.

Critical Appraisal of the Milwaukee Protocol for Rabies: This Failed Approach Should Be Abandoned.

The Milwaukee protocol has been attributed to survival in rabies encephalitis despite a lack of scientific evidence supporting its therapeutic measures. We have reviewed the literature with reference to specific treatment recommendations made within the protocol. Current literature fails to support an important role for excitotoxicity and cerebral vasospasm in rabies encephalitis. Therapies suggested in the Milwaukee protocol include therapeutic coma, ketamine infusion, amantadine, and the screening/prophylaxis/management of cerebral vasospasm. None of these therapies can be substantiated in rabies or other forms of acute viral encephalitis. Serious concerns over the current protocol recommendations are warranted. The recommendations made by the Milwaukee protocol warrant serious reconsideration before any future use of this failed protocol.

Medical treatment of horses with deep digital flexor tendon injuries diagnosed with high-field-strength magnetic resonance imaging: 118 cases (2000-2010).

To describe the location and severity of deep digital flexor tendon (DDFT) lesions diagnosed by means of high-field-strength MRI in horses and to identify variables associated with return to activity following medical treatment. Retrospective case series. 118 horses. Medical records of horses with DDFT injury diagnosed with MRI over a 10-year period (2000-2010) and treated medically (intrasynovial administration of corticosteroids and sodium hyaluronan, rest and rehabilitation, or both) were reviewed. History, signalment, use, results of lameness examination and diagnostic local anesthesia, MRI findings, and treatment details were recorded. Outcome was obtained by telephone interview or follow-up examination. Horses were grouped by predictor variables and analyzed with logistic regression to identify significant effects. Overall, of 97 horses available for follow-up (median time to follow-up, 5 years; range, 1 to 12 years), 59 (61%) returned to activity for a mean duration of 22.6 months (median, 18 months; range, 3 to 72 months), with 25 (26%) still sound at follow-up. Of horses with mild, moderate, and severe injury, 21 of 29 (72%), 20 of 36 (56%), and 18 of 32 (56%), respectively, returned to use. Horses treated with intrasynovial corticosteroid injection and 6 months of rest and rehabilitation returned to use for a significantly longer duration than did horses treated without rest. Western performance horses returned to use for a significantly longer duration than did English performance horses. Results of the present study suggested that outcome for horses with DDFT injuries treated medically depended on injury severity, presence of concurrent injury to other structures in the foot, type of activity, and owner compliance with specific treatment recommendations. Although some horses successfully returned to prior activity, additional treatment options are needed to improve outcome in horses with severe injuries and to improve long-term prognosis.

Microbiology of healthcare-associated infections and the definition accuracy to predict infection by potentially drug resistant pathogens: a systematic review.

BackgroundHealthcare-associated infections (HCAI) represent up to 50 % of all infections among patients admitted from the community. The current review intends to provide a systematic review on the microbiological profile involved in HCAI, to compare it with community-acquired (CAI) and hospital-acquired infections (HAI) and to evaluate the definition accuracy to predict infection by potentially drug resistant pathogens.MethodsWe search for HCAI in MEDLINE, SCOPUS and ISI Web of Knowledge with no limitations in regards to publication language, date of publication, study design or study quality. Only studies using the definition by Friedman et al. were included. This review was registered at PROSPERO Systematic Review Registration with the Number CRD42014013648.ResultsA total of 21 eligible studies with 12,096 infected patients were reviewed; of these 3497 had HCAI, 2723 were microbiologically documented. Twelve studies were on pneumonia involving 1051 patients with microbiological documented HCAI, the application of the current guidelines for this group of patients would result in an appropriate antibiotic therapy in 95 % of cases at the expense of overtreatment in 73 %; the application of community-acquired pneumonia guidelines would be adequate in only 73–76 % of the cases; an alternative regimen with piperacillin-tazobactam or aztreonam plus azithromycin would increase antibiotic adequacy rate to 90 %. Few studies were found on additional focus of infection: endocarditis, urinary, intra-abdominal and bloodstream infections. All studies included in this review showed an association of the HCAI definition with infection by PDR pathogens when compared to CAI [odds ratio (OR) 4.05, 95 % confidence interval (95 % CI) 2.60–6.31)]. The sensitivity of HCAI to predict infection by a PDR pathogen was 0.69 (0.65–0.72), specificity was 0.67 (0.66–0.68), positive likelihood ratio was 1.9 and the area under the summary ROC curve was 0.71.ConclusionsThis systematic review provides evidence that HCAI represents a separate group of infections in terms of the microbiology profile, including a significant association with infection by PDR pathogens, for the main focus of infection. The results provided can help clinician in the selection of empiric antibiotic therapy and international societies in the development of specific treatment recommendations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1304-2) contains supplementary material, which is available to authorized users.